Microbial flora in persons with HIV likely play an important role in various diseases, but the nature of the microbiome in the lungs of persons with HIV has not been studied. High-throughput, DNA sequencing technologies now allow examination of complex microbial communities including organisms that cannot be cultured. These techniques have potential to yield important information about events in the lung during HIV and its associated pulmonary disorders. Chronic obstructive pulmonary disease (COPD) is of particular interest in the current era of HIV infection. Pathogenesis of HIV-associated COPD is poorly understood, but one or more infections may upregulate expression of HIV in the lungs, amplify the pulmonary inflammatory response, and lead to release of proteases or pro-apoptotic factors. Data from our group suggest that low level infection with Pneumocystis is increased in HIV-F subjects and associated with anatomic emphysema. Other infections alone or in combination are likely to be important in disease pathogenesis. Application of metagenomic techniques will allow us to determine patterns and changes in the population of microbes that play a key role in the pathogenesis and progression of emphysema in this population. The overall goals of this proposal are to determine the respiratory microbial flora (or microbiota) in HIV-I- and HIV- subjects and to establish its role in pathogenesis and progression of HIV-associated COPD using our ongoing cohorts. Specific aims of the proposal are: 1. To compare the microbial community structure in the respiratory tract in subjects with and without HIV infection. 2. To test the hypothesis that the respiratory microbiome in HIV-I- subjects with COPD differs from that in HIV-f subjects without COPD and is related to COPD progression. 3. To test the hypothesis that bacterial products in the blood are detectable in HIV-f subjects with COPD and are associated with immune activation. We will perform oral wash, sputum induction, bronchoscopy, and blood draws in HIV- and HIV-I- subjects and carry out high-throughput virus metagenomics and bacterial, fungal and protozoal 16S rDNA analyses for characterization of microbiome population diversity. Results will be used to determine which microbes are present, their relative proportions, their location, and their relationship to HIV and COPD. RELEVANCE (See instructions): This proposal will help us determine which infections are present In the lungs of people with HIV and how the infections might explain why HIV-infected individuals develop emphysema faster than non-HIV-infected people. This information will help us understand and treat emphysema in these patients and in the many non-HIV-infected people who suffer from emphysema.